Cetylpyridinium chloride

Endpoint summary

Description of key information

CPC demonstrates local irritation when administered orally to rats in a chronic study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

5 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

adequate

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The toxicity of CPC has been well studied in repeated dose exposure in rats and dogs. In both 28 -day and 6 month studies, the primary target of toxicity is the nonglandular stomach, where there is evidence of localized irritation, with histological evidence of inflammation, erosion and necrosis of the gastric mucosa. Distention of the cecum is also commonly seen, as is inflammation of the esophagus and, occasionally, the buccal mucosa, perhaps associated with aspiration of the irritating substance. There is no histological evidence of systemic toxicity after chronic oral exposure. Similar conclusions are observed after 28 days of oral treatment to rats and Beagle dogs. At chronic doses of 15 mg/kg bw/d and higher, rats exhibit decreased body weight gain and decreased food consumption, suggesting that CPC indirectly, through a mechanism of chronic irritation and associated stress, leads to systemic adverse effects. Toxicokinetic studies indicate CPC is rapidly eliminated from the body after oral exposure, primarily in the feces. At the concentration of 5 mg/kg bw/d after 6 months of exposure, no evidence of gastrointestinal irritation is seen; 5 mg/kg bw/d is chosen as a very conservative No Adverse Effect Level (NOAEL).

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Justification for classification or non-classification

CPC is not classified for repeated dose toxicity (specific target organ toxicity), even though gastrointestinal irritation is observed after repeated exposure. According to Regulation EC No. 1272/2008, STOT-RE is a classification for effects other than those evaluated for other effects, as set forth in Section 3.9.1 (relating to Sections 3.1 to 3.8, and 3.10). CPC is classified for acute oral toxicity, acute inhalation toxicity, and dermal irritation. No systemic toxicity unrelated to these findings is established and hence, CPC is not classified for STOT-RE.